拉米夫定耐药慢性乙型肝炎患者HBV P基因区突变序列分析

Mutations of HBV polymerase gene sequence in lamivudine-resistant chronic hepatitis B patients

目的探讨拉米夫定耐药慢性乙型肝炎(CHB)患者HBVP基因逆转录酶区(RT区)序列突变特点。方法收集115例接受拉米夫定治疗的CHB患者的临床资料,采用PCR产物直接测序法检测HBVP基因RT区序列耐药变异。结果入选的115例患者中103例检测到拉米夫定基因型耐药变异,最主要的耐药变异模式为rtL180M+rtM204V和rtM204I,分别占58.3%和22.3%,其他耐药位点包括rtL80V/I、rtT184S和rtA200V,并在5例患者中检测到RT区3个位点的联合变异。结论对拉米夫定治疗患者的耐药检测除了HBVP基因区常见的rtL180和rtM204位点变异外,还应考虑其他位点的联合耐药变异。

Objective To explore the characteristics of mutation in HBV polymerase （P） gene reverse transcriptase region （RT region） in lamivudine-resistant chronic hepatitis B （CHB） patients. Methods This study involved 115 CHB patients who developed clinical resistance to lamivudine. Direct sequencing of the PCR products was used to detect lamivudine genotypic resistance. Results Lamivudine resistant mutation was detected in 103 patients, and the major mutations included rtL180M＋rtM204V and rtM204I, accounting for 58.3% and 22.3%, respectively. Other resistant substitutions included rtL80V/I, rtT184S, and rtA200V, and combined mutation of triple resistant substitutions was detected in HBV RT region of 5 patients by direct sequencing. Co.nclusion For lamivudine-treated patients, combined mutation at the sites other than rtL180 and rtM204 in HBV P gene should also be detected for drug resistance evaluation.